Imaging of vaginal bleeding in early pregnancy

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Bleeding during the first trimester of pregnancy is common. Although
usually of no permanent consequence, it can be a sign of complication,
such as a threatened abortion or a failed intrauterine pregnancy, or
other serious pathology, such as ectopic pregnancy or gestational
trophoblastic disease. Familiarity with the imaging patterns of these
entities is important, as misdiagnosis can lead to harm to the mother,
fetus, or both. This review will focus on the most common causes of
bleeding in the first trimester, their imaging appearances, and
diagnostic algorithms.

Imaging in pregnancy

Radiology plays an essential role in identifying and diagnosing early
pregnancy complications, with ultrasound (US) being the primary imaging
modality. Nearly all instances of first trimester bleeding can be
adequately evaluated with a combination of clinical evaluation, serum
β-hCG assay and US, preferably via endovaginal technique. Magnetic
resonance imaging has a limited role, particularly if the US is
technically inadequate, or in the setting of an indeterminate adnexal
mass. There is essentially no role for CT in evaluating first trimester
bleeding. These recommendations and further discussion are outlined in
the most recent revision of the ACR Appropriateness Criteria for First
Trimester Bleeding (Table 1).1

Ultrasound images can be obtained via transabdominal or endovaginal
approaches; usually both are utilized in tandem. Transabdominal scanning
is usually obtained first, with a lower-frequency curved or vector
transducer, typically 4-6 MHz. This provides a large field of view,
optimal to demonstrate large or widespread processes such as large
adnexal masses or hemoperitoneum. Endovaginal US is usually required for
a more detailed evaluation of the uterus and ovaries. Endovaginal
probes utilize a higher frequency, typically 8-10 MHz, yielding
increased resolution at the expense of less tissue penetration. Because
accurate measurements of early gestational processes are crucial,
endovaginal imaging should be utilized whenever possible. For this
review, all size references are based on endovaginal measurements unless
otherwise specified.

Normal early development

Decidual reaction appears first

Although the first trimester begins at the first day of the last
menstrual period, fertilization occurs approximately two weeks later,
marking the beginning of the conceptus period of the first trimester
(3-5 weeks menstrual age). Implantation of the blastocyst into the
endometrium occurs during the fourth menstrual week, at which point the
endometrium is referred to as the decidua.2 During this time
the very early chorionic sac may be visible as a small fluid-filled sac
with an echogenic rim located eccentrically within the endometrium,
known as the “intradecidual sign” (Figure 1).3 This can be
seen as early as 4.5 weeks, and is nearly 100% specific for an
intrauterine pregnancy (IUP), although it is only 60-68% sensitive.4
This precedes the “double decidual sign,” which consists of two
concentric echogenic rings: the decidua capsularis surrounding the
gestational sac, and the decidua parietalis representing the opposite
wall of the endometrium, often separated by a thin collection of fluid
within the endometrial cavity (Figure 2).5 As with the
intradecidual sign, the double decidual sign is highly specific but
insensitive; furthermore, a yolk sac may be visible before this sign is
apparent, making it less useful in confirming an early IUP. Importantly,
one should differentiate these two early signs of an IUP from a fluid
collection within the endometrial canal, the “pseudo-gestational sac”
(Figure 3).

Yolk sac appearance

The yolk sac is the first structure able to be visualized within the
early gestational sac (chorionic sac), usually by the time the mean
gestational sac diameter (MSD) is 8-10 mm (Figure 4).6 A
normal yolk sac is always less than 6 mm in diameter; a yolk sac greater
than 6 mm is nearly 100% specific for an abnormal pregnancy.7 Shortly
following appearance of the yolk sac, the embryo is usually apparent at
approximately 6 weeks, when the MSD is greater than 16 mm, as a small
echogenic structure along one side of the yolk sac. Cardiac activity can
usually be identified by the time the embryo is visible.

Amnion and embryo formation

Formation of the amniotic sac coincides with formation of the yolk
sac, but is usually not visible at this early stage secondary to its
very thin membrane. By 7 weeks’ gestational age, the amniotic sac
becomes visible as it fills with fluid and separates from the embryo
(Figure 5). By the time the amniotic sac is visible, the embryo can be
readily identified; the absence of an embryo, or “empty amnion sign,” is
highly specific for a failed pregnancy (Figure 6).8 As the amniotic sac enlarges, it gradually obliterates the chorionic sac, with complete fusion by 12 weeks gestational age.9

In the absence of visualization of any of the above in the setting of
a positive urine or serum β-hCG, the pregnancy should be considered a
pregnancy of unknown location, or PUL.

Failed intrauterine pregnancy

Familiarity with the specific US criteria for diagnosing a failed or
anembryonic pregnancy (“blighted ovum”) (Figure 6) is essential. The
traditionally taught size discriminatory thresholds for declaring an
abnormal pregnancy have been called into question,10 and the
Society of Radiologists in Ultrasound has subsequently adopted revised
criteria; the results of their consensus conference statement have
recently been published.11 In brief, a major reason for the
updated criteria was to increase the specificity of the imaging
diagnosis of a failed IUP to prevent the unwanted termination of very
early but potentially viable pregnancies.

The traditional radiologic teaching has been a “multiple of 5’s”
rule: 1) a yolk sac should be visible when the mean gestational sac
diameter (GSD) is >10 mm; 2) an embryo should be visible when the
mean GSD is >15; and 3) a heartbeat should be present when the crown
rump length (CRL) of the embryo is >5 mm. While likely indicating an
abnormal pregnancy, they are not specific. Strict adherence to these
criteria will uncommonly result in the false diagnosis of a failed
pregnancy when in fact there is a potentially viable pregnancy that
could be harmed by intervention. The revised criteria for diagnosing
pregnancy failure are as follows (Table 2).11 Note the increase in CRL and mean GSD size thresholds, below which a failed pregnancy should not be diagnosed.

One of the most important new concepts is that the diagnosis of a
failed pregnancy should not be made based on a single elevated β-hCG
measurement in the setting of a PUL. Normal pregnancies can develop
subsequent to an ultrasound without an IUP and β-hCG greater than the
traditional discriminatory threshold of 2000 or even 3000 mIU/mL.12,13
Therefore, the diagnosis of a failed or ectopic pregnancy should never
be based on a single β-hCG measurement in the absence of definitive US
findings.

Threatened abortion

The term “threatened abortion” applies to any pregnancy of less than
20 weeks with abnormal bleeding, pain or contractions, with a closed
cervix. Bleeding occurs in up to 27% of pregnancies, with the subsequent
risk of miscarriage approximately 12%.14

Subchorionic bleed

Subchorionic, or perigestational, hemorrhage is present in approximately 20% of women presenting with a threatened abortion,15
and is the most common cause of bleeding in normal IUPs, usually
presenting in the late first trimester. On US, these appear as either
hyperechoic or hypoechoic, depending upon the age of the blood products
(Figure 7). Most often these are not associated with any significant
clinical sequelae, particularly if fetal cardiac activity is present.
Large bleeds, defined as involving more than 2/3 the circumference of
the gestational sac, are more likely to result in pregnancy failure
(Figure 8).16 For smaller hematomas, no size thresholds have been confirmed to be prognostic,17 although this finding is a risk factor for subsequent pregnancy complications.18,19

Ectopic pregnancy

Ectopic pregnancy accounts for 2% of all pregnancies, as last
reported by the U.S. Centers for Disease Control and Prevention in 1992.20
The incidence is higher in patients with a history of prior ectopic
pregnancy, tubal disease, presence of an intrauterine device, and in
those undergoing in vitro fertilization.21 The classic
clinical triad is pain, bleeding, and adnexal mass; however these are
present only in a minority of cases. The vast majority of ectopic
pregnancies occur within the fallopian tube (tubal ectopic). Less common
locations include interstitial (cornual), cervical, within a cesarean
section scar, or ovarian. Occasionally, the only US finding will be free
fluid.

Tubal pregnancy

Visualization of a live embryo outside of the uterine cavity is 100%
specific for ectopic pregnancy, but is rarely encountered in practice.
More often, an adnexal tubal ring is identified. On US this consists of
an echogenic ring with central fluid, separate from the ovary. The ring
may or may not contain a yolk sac or embryo. The ring is typically more
echogenic than the ring of a corpus luteum, with which it can
potentially be confused (Figure 9).22,23 Distinguishing
between the two is vital, as the misdiagnosis of a corpus luteum as an
ectopic pregnancy in the setting of PUL can have tragic consequences.
Endovaginal transducer pressure on the ovary can help determine if the
lesion is within or separate from the ovary. As ovarian ectopic
pregnancies are exceedingly rare, demonstrating an intra-ovarian
location confirms a corpus luteum and essentially excludes an ectopic
mass.

Often, the ectopic may be identified only as an extra-ovarian adnexal
mass, without the classic ring-like appearance, because of hemorrhage.
While the presence of color flow helps to confirm an ectopic pregnancy
mass, the converse is not always true. Not all ectopics are vascular,
and the absence of color Doppler flow does not exclude an ectopic
pregnancy. While large amounts of hemorrhage typically indicate a
ruptured ectopic, occasionally a ruptured hemorrhagic cyst can present
with a similar clinical and US picture.

Interstitial pregnancy

When an ectopic pregnancy implants within the interstitial segment of
the fallopian tube, it is termed an interstitial (or cornual) ectopic.
These can be mistaken for IUP if not fully investigated, as they can
have a normal interface with the endometrium along their inner margin.
Additionally, the distinction from tubal ectopics is important, as
cornual pregnancies have an increased risk of severe hemorrhage and
mortality.

The interstitial location can be identified by the eccentric location
high within the uterus, as well as by the presence of only a thin
mantle of myometrium along the outer margin, usually less than 5 mm
thick.24,25 An additional feature that can be helpful is the
“interstitial line sign,” representing a thin echogenic line extending
from the endometrial canal directly to the gestational sac, representing
the cornual segment of the endometrial canal or interstitial portion of
the fallopian tube (Figure 10).26

Cervical pregnancy

As with interstitial ectopic pregnancies, the risk of significant
bleeding and mortality is increased with cervical ectopics relative to
tubal ectopics. The gestational sac in a cervical ectopic pregnancy must
be distinguished from a gestational sac passing through the cervix
during an abortion in progress. In the case of a cervical ectopic, the
gestational sac usually maintains its normal round or slightly ovoid
shape. Additionally, the presence of perigestational blood flow on color
Doppler can aid in the distinction (Figure 11).27,28 A passing gestational sac has a crenated or elongated appearance with no embryonic cardiac activity (Figure 12).29

Cesarean section scar pregnancy

Pregnancies implanted at the cesarean section scar site frequently
result in spontaneous miscarriage (44%), but are at increased risk of
developing placenta previa and placenta accreta if they develop later
into pregnancy, and are associated with increased risk of severe
hemorrhage at delivery.30 Diagnosis is easier to establish in
the first trimester, when there is an empty uterine cavity, a
gestational sac implanted anteriorly at the level of the cervical os or
at the visible or presumed cesarean section scar site, and
perigestational Doppler flow (Figure 13).

Management of ectopic pregnancies

Ectopic pregnancy can be managed medically or surgically. Imaging
features that influence management include the size of the ectopic;
presence of embryonic cardiac activity, pelvic hemorrhage or tubal
rupture; and the location of the ectopic. Nonsurgical techniques include
systemic methotrexate or ultrasound-guided local injection of
methotrexate or KCl. For tubal ectopics, salpingostomy or salpingectomy
may be performed. Interstitial ectopics may require cornual resection or
hysterectomy. Cesarean section or cervical ectopics may require a
combination of medical and surgical therapy.

Vascular causes of bleeding

Retained products of conception

Retained products of conception (RPOC) can be found following
therapeutic or spontaneous abortion, as well as post-partum. Following
first-trimester abortion, there is typically normal or mildly elevated
β-hCG. The presence of a retained gestational sac is not a diagnostic
dilemma but is rarely encountered. The presence of blood flow within a
thickened endometrium, particularly when associated with a visible mass,
is highly suggestive of RPOC (Figure 14). However, the absence of
Doppler flow does not necessarily exclude RPOC. Unfortunately there is
no definitive endometrial thickness threshold that is entirely specific;
however a thickness <10mm likely excludes the possibility of
clinically significant RPOC.31

Arteriovenous malformation

Arteriovenous malformations (AVMs) of the uterus can be either
congenital or acquired; and can be encountered in the setting of prior
therapeutic abortion, dilatation and curettage, cesarean section or
invasive tumor such as endometrial carcinoma or gestational
trophoblastic disease.17 AVMs can be comprised of a single
arteriovenous fistula (AVF) or a complex structure of multiple vessels.
US usually demonstrates a complex mass, with color Doppler revealing
internal flow (Figure 15). Spectral Doppler demonstrates low-resistance
arterial waveforms and pulsatile venous waveforms consistent with
vascular shunting.32

There is frequently overlap in the ultrasound appearance of AVMs and
RPOC, and the distinction is not always possible. RPOC tend to be
located within the endometrium, with AVMs in the myometrium; however,
the presence of heterogeneous blood within the endometrial cavity can
obscure the myometrial margins or mimic RPOC. Clinical history and serum
β-hCG are helpful in differentiating these two entities.

Gestational trophoblastic disease

Bleeding is one of the most common clinical presentations of this
spectrum of disorders that includes hydatidiform mole, invasive mole,
and choriocarcinoma. The hallmark is excessive production of β-hCG.
Other classic signs of a rapidly enlarging uterus, hyperemesis
gravidarum, and pre-eclampsia are more common in the second trimester.33

Hydatidiform mole

Complete hydatidiform mole is the most common of these entities. On
US, the classic “cluster of grapes” appearance is often not present in
the first trimester and appearance is variable. Findings may include a
small echogenic mass without cystic spaces or a mixed solid and cystic
mass within the endometrium.34 Theca lutein cysts in the
ovaries result from increased β-hCG production, but are usually not
present until the second trimester. Being avascular, color flow is
typically not helpful in diagnosing a complete hydatidiform mole (Figure
16).35

Invasive mole/choriocarcinoma

The distinction between non-invasive mole and invasive
mole/choriocarcinoma is not always possible with US. In contrast to
hydatidiform moles, invasive moles and choriocarcinomas demonstrate
color flow on Doppler, with low-impedance waveforms (Figure 17).35
Invasive moles grow deep into the myometrium, sometimes with
penetration into parametrial tissues and peritoneum, but rarely
metastasize. In contrast, choriocarcinoma readily metastasizes to the
lungs and less frequently the pelvis,17 for which CT is useful (Figure 18). Magnetic resonance imaging may aid in evaluating persistent residual disease in the pelvis.

Conclusion

Ultrasound can readily distinguish the most common causes of vaginal
bleeding in early pregnancy, and plays an essential role in patient
management. Familiarity with the US appearance as well as new guidelines
is essential to avoid causing potential harm to the mother or
developing fetus.